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SAT0445 Short-term effects of secukinumab on bone turnover markers and wnt signaling antagonists in patients with psoriatic arthritis
  1. A Fassio,
  2. L Idolazzi,
  3. O Viapiana,
  4. C Benini,
  5. E Vantaggiato,
  6. M Rossini,
  7. D Gatti
  1. Rheumatology, Aoui Verona Reumatologia, Verona, Italy

Abstract

Background psoriatic arthritis (PsA) is a chronic inflammatory disease characterized also by increased levels of cells producing IL-17 [1], and these levels have been shown to correlate with measures of disease activity and structural damage and bone loss [2]. Secukinumab is a new monoclonal antibody licensed woth the treatment of PsA which selectively binds to and neutralizes interleukin-17 (IL-17). Currently, data about the effects on the activity of either bone-reabsorbing cells and bone-forming cells secondary to the inhibition of the IL-17 pathway are completely absent.

Objectives the aim of our study was to explore the short-term effects of secukinumab on bone turnover markers (BTM) and Dkk-1 and sclerostin.

Methods we enrolled 28 patients with PsA, classified with the CASPAR criteria and 43 healthy controls (HC). For the PsA group DAS28 was recorded and serum samples were stored at baseline and then at the first, the third and the sixth month of therapy. Intact N-propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I). Dickkopf-related-protein 1 (Dkk-1) and sclerostin were dosed too. For the HC group, a single blood sample was taken.

Results Neither P1NP nor CTX showed any statistically significant variation. Baseline Dkk-1 for the PsA group was lower than HC. Both Dkk-1 and sclerostin demonstrated a significant increase at the sixth month. When the PsA groups was compared to HC, the difference between the levels of Dkk-1 lost significance at month six.

Table 1

Conclusions our study demonstrated that the treatment with secukinumab has little influence on the levels of BTM within the first six months of treatment but a definite influence on some fine regulators of the bone cells activity such as the WNT inhibitors and it is able, in some way, to normalize the Dkk-1 levels in PsA patients. The clinical implications of this trend are currently unclear thought it might suggest an drug-induced inhibition of the over-proliferation of bone typical of the joint lesions of PsA. Further studies with greater numbers of patients are warranted to determine whether these preliminary results have clinical relevance.

References

  1. Jandus C, Bioley G, Rivals J-P, et al. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 2008;58:2307–17. doi:10.1002/art.23655.

  2. Uluçkan Ö, Jimenez M, Karbach S, et al. Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Sci Transl Med 2016;8:330ra37. doi:10.1126/scitranslmed.aad8996.

References

Disclosure of Interest None declared

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